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A proof-of-concept study in small and large animal models for coupling liver normothermic machine perfusion with mesenchymal stromal cell bioreactors

Author

Listed:
  • Umberto Cillo

    (University of Padua)

  • Caterina Lonati

    (Via Pace 9)

  • Alessandra Bertacco

    (University of Padua)

  • Lucrezia Magnini

    (Via Pace 9)

  • Michele Battistin

    (Via Pace 9)

  • Lara Borsetto

    (University of Padua)

  • Francesco Dazzi

    (King’s College London)

  • David Al-Adra

    (School of Medicine and Public Health, University of Wisconsin)

  • Enrico Gringeri

    (University of Padua)

  • Maria Laura Bacci

    (University of Bologna)

  • Andrea Schlegel

    (Via Pace 9
    Cleveland Clinic)

  • Daniele Dondossola

    (Via Francesco Sforza 35
    Via Francesco Sforza 35)

Abstract

To fully harness mesenchymal-stromal-cells (MSCs)’ benefits during Normothermic Machine Perfusion (NMP), we developed an advanced NMP platform coupled with a MSC-bioreactor and investigated its bio-molecular effects and clinical feasibility using rat and porcine models. The study involved three work packages: 1) Development (n = 5): MSC-bioreactors were subjected to 4 h-liverless perfusion; 2) Rat model (n = 10): livers were perfused for 4 h on the MSC-bioreactor-circuit or with the standard platform; 3) Porcine model (n = 6): livers were perfused using a clinical device integrated with a MSC-bioreactor or in its standard setup. MSCs showed intact stem-core properties after liverless-NMP. Liver NMP induced specific, liver-tailored, changes in MSCs’ secretome. Rat livers exposed to bioreactor-based perfusion produced more bile, released less damage and pro-inflammatory biomarkers, and showed improved mithocondrial function than those subjected to standard NMP. MSC-bioreactor integration into a clinical device resulted in no machine failure and perfusion-related injury. This proof-of-concept study presents a novel MSC-based liver NMP platform that could reduce the deleterious effects of ischemia/reperfusion before transplantation.

Suggested Citation

  • Umberto Cillo & Caterina Lonati & Alessandra Bertacco & Lucrezia Magnini & Michele Battistin & Lara Borsetto & Francesco Dazzi & David Al-Adra & Enrico Gringeri & Maria Laura Bacci & Andrea Schlegel &, 2025. "A proof-of-concept study in small and large animal models for coupling liver normothermic machine perfusion with mesenchymal stromal cell bioreactors," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55217-7
    DOI: 10.1038/s41467-024-55217-7
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